Schotten U, Koenigs B, Rueppel M, Schoendube F, Boknik P, Schmitz W, Hanrath P
Department of Cardiology, Medical Faculty, University of Technology, Pauwelsstrasse 30, Aachen, D-52057, Germany.
J Mol Cell Cardiol. 1999 Aug;31(8):1483-94. doi: 10.1006/jmcc.1999.0981.
Pathological intracellular calcium handling has been proposed to underlie the alterations of contractile behavior in hypertrophied myocardium. However, the myocardial protein expression of intracellular calcium transport proteins in compensated human left ventricular hypertrophy has not yet been studied. We investigated septal myocardial specimens of patients suffering from hypertrophic obstructive cardiomyopathy (n=14) or from acquired aortic valve stenosis (n=11) undergoing myectomy or aortic valve replacement, respectively. For comparison, we studied non-hypertrophied myocardium of six non-failing hearts which could not be transplanted for technical reasons. The myocardial density of the calcium release channel of the sarcoplasmic reticulum (SR) was determined by(3)H-ryanodine binding. Myocardial contents of SR Ca(2+)-ATPase, phospholamban, calsequestrin and Na(+)/Ca(2+)-exchanger were analysed by Western blot analysis. The myocardial SR calcium release channel density was not significantly different in hypertrophied and non-failing human myocardium. In both hypertrophic obstructive cardiomyopathy and in aortic valve stenosis, SR Ca(2+)-ATPase expression was reduced by about 30% compared to non-failing myocardium (P<0.05), whereas the expression of phospholamban, calsequestrin, and the Na(+)/Ca(2+)-exchanger was unchanged. The decrease of SR Ca(2+)-ATPase expression was still observable when related to its regulatory protein phospholamban or to the myosin content of the homogenates (P<0.05). Furthermore, the SR Ca(2+)-ATPase expression was inversely correlated to the septum thickness assessed by echocardiography, but not to age, cardiac index or outflow tract gradient. In primary as well as in secondary hypertrophied human myocardium, the expression of SR Ca(2+)-ATPase is reduced and inversely related to the degree of the hypertrophy. The diminished SR Ca(2+)-ATPase expression might result in reduced Ca(2+)reuptake into the SR and might contribute to altered contractile behavior in hypertrophied human myocardium.
病理性细胞内钙处理被认为是肥厚心肌收缩行为改变的基础。然而，代偿性人类左心室肥厚时细胞内钙转运蛋白的心肌蛋白表达尚未得到研究。我们分别调查了接受肌切除术或主动脉瓣置换术的肥厚性梗阻性心肌病患者（n = 14）或获得性主动脉瓣狭窄患者（n = 11）的间隔心肌标本。作为对照，我们研究了因技术原因无法移植的六个非衰竭心脏的非肥厚心肌。通过³H-ryanodine结合测定肌浆网（SR）钙释放通道的心肌密度。通过蛋白质免疫印迹分析来分析SR Ca²⁺-ATP酶、受磷蛋白、肌集钙蛋白和Na⁺/Ca²⁺交换体的心肌含量。肥厚性和非衰竭性人类心肌中的心肌SR钙释放通道密度没有显著差异。在肥厚性梗阻性心肌病和主动脉瓣狭窄中，与非衰竭心肌相比，SR Ca²⁺-ATP酶表达均降低约30%（P<0.05），而受磷蛋白、肌集钙蛋白和Na⁺/Ca²⁺交换体的表达没有变化。当与其调节蛋白受磷蛋白或匀浆中的肌球蛋白含量相关时，SR Ca²⁺-ATP酶表达的降低仍然可以观察到（P<0.05）。此外，SR Ca²⁺-ATP酶表达与通过超声心动图评估的间隔厚度呈负相关，但与年龄、心脏指数或流出道梯度无关。在原发性和继发性肥厚性人类心肌中，SR Ca²⁺-ATP酶的表达均降低，并且与肥厚程度呈负相关。SR Ca²⁺-ATP酶表达的减少可能导致Ca²⁺再摄取到SR中的减少，并可能导致肥厚性人类心肌收缩行为的改变。
